This proposal is to request support for a Keystone Symposia meeting entitled *Metabolic Pathways of Longevity*, organized by Arlan G. Richardson, Eva L. Feldman and Nir Barzilai, which will be held in Copper Mountain, Colorado from March 30th -April 4, 2008. This meeting brings together leading investigators in aging and diabetes to discuss how alterations in insulin/IGF-I signaling affect longevity, and the similarities between insulin resistance and aging. Data emerging from several areas suggest that insulin and insulin-like growth factor (IGF-I) could be key players in the regulation of longevity in organisms as diverse as invertebrates and humans. Caloric restriction, which retards aging, is shown to reduce plasma levels of insulin and IGF-I, and the disruption of the insulin/IGF-I receptor in nematodes and flies is shown to increase lifespan. However, mammals with genetic or acquired defects in the insulin signaling pathway are at risk for age-related diseases and increased mortality, e.g., insulin resistance and diabetes. [unreadable] [unreadable] PROJECT NARRATIVE: Over the past 5 to 10 years, it has become apparent that alterations in some metabolic pathways, e.g., insulin/IGF-I, can extend life span and retard aging. The Keystone Symposia Metabolic Pathways of Longevity meeting is timely because of the large amount of information generated recently in this area, and because of the potential importance of metabolic pathways as therapeutic targets to improve the quality of life and potentially alter aging and age-related diseases. [unreadable] [unreadable] [unreadable]